Over the past few decades, many studies have found significant sex differences in the prevalence, symptoms, and severity of brain-related disorders, including depression, schizophrenia, and multiple sclerosis. The scientific community also has documented sex differences in how people with these disorders respond to certain treatments. To date, despite calls for more rigorous balancing of sexes in research projects, most preclinical studies continue to rely solely on male cells, tissues, and participants. Now, however, the National Institutes of Health (NIH) is calling for a "sea change" in research practices, issuing new policies that require that sex differences be addressed in future biomedical research programs funded by the agency.
A call for change
Janine Clayton, the head of the NIH's Office of Research on Women's Health (ORWH), and Francis Collins, director of the NIH, introduced the new policies in a comment piece in the May 14 issue of Nature. The two cited several cases where discovery of sex differences has led to policy change in the medical community, including the Food and Drug Administration's recent decision to cut the recommended dose of the sleep drug Ambien by half for female patients. Clayton and Collins outlined their new approach to address sex differences in biomedical research, including a policy calling for inclusion of females and males in NIH-funded projects.
"This is a really essential issue. The lack of sex differences [research] means there are real gaps, startling gaps in our knowledge of health. So it's an issue that we are attacking from multiple sides to make sure that we can address it properly," says Clayton. "We start with policy, because that tells us how to move forward. We are also developing training modules to give the scientific community the tools they need to learn how to do this when they are considering experimental design. And we are also partnering with publishers because publications are 'the point of the realm' and are vital to getting the right information out there. It's what is needed so everyone understands that sex is a fundamental variable in biomedical research-and it can't be ignored any longer."
The NIH initiative is "huge," says Jill Goldstein, director of research for the Connors Center for Women's Health and Gender Biology at Harvard Medical School. "I've been doing work in sex differences for 30 years now," she says. "This is the kind of call to action that those of us who have worked in this area have hoped to see for quite some time. And, frankly, it's something we need to see in preclinical research, so we can be sure we are serving everyone, both men and women, in medicine."
Sexism and funding
While most have heralded the NIH for this push, others have suggested that the new policies could have unintended consequences. Some have called on the so-called "Larry Summers" argument , saying that a focus on sex as a fundamental variable could result in scientific sexism. Larry Cahill, a researcher who studies sex differences in the brain at the University of California at Irvine, says that argument is nonsense.
"We shouldn't be concerned with the supposed sexism that may exist if we pursue the truth about sex differences in the brain. What we should be concerned with, and what this policy addresses, is the sexism that exists today," he says. "Right now, there is an unequal treatment of men and women in medicine-especially of women-because we are insisting that women be treated the same way as men. Not looking at sex differences, especially when we are talking about medicine and healthcare, is just indefensible at this point."
But while both Cahill and Goldstein are excited about NIH's new position, they hope the organization will support the new policies they are mandating with enough funding to get the job done.
"The new policy is an important first step. But there must be funding associated with these mandates so people can comply," says Goldstein. "Money is a critical component of all this. There has to be funding to focus on sex differences or else it's hard to see how it is really going to happen."
Fomenting a "sea change"
The number of studies documenting important sex differences in the prevalence and prognosis of disease has grown only in the past decade. But while it would be easy to say the NIH's new policies are just based on science, Cahill notes that there has been a "critical mass" reached beyond the laboratory, too. Goldstein concurs.
"This is the most significant response from a government organization in over 20 years regarding sex differences in medicine," says Goldstein. "And I believe it's the culmination of a lot of research but also the culmination of advocacy, changes in how the FDA evaluates clinical trials, news reports, questions from Congress, and even the Affordable Care Act looking at the efficacy and cost of various treatments. We have a lot of data that we just can't ignore anymore."
Clayton hopes the new policies will foment a "sea change," particularly in preclinical research. She says that while people have been talking about sex differences for quite some time, there has not been a lot of real change in how they do the science. There is still a primary focus on male participants and cells.
"We've seen a lot of sex differences recorded sporadically in the scientific literature. But by bringing NIH into the picture, we can work together with the scientific and medical community to put some real energy behind this," she says. "We want a more uniform adoption-to have people really understand why sex differences are such a fundamental variable in research. By doing that, we have the opportunity to address some serious gaps in our knowledge of disease and treatment. And that's how we get to the point in research so men and women can get the full benefit and improved health."